title: Atorvastatin upregulates regulatory T cells and reduces clinical disease activity in patients with rheumatoid arthritis.
abstract: In this study, we investigated the hypothesis that regulatory T cells (T(reg)) are involved in the immunomodulatory effects of statins on rheumatoid arthritis (RA) patients. The 12-week study cohort consisted of 55 RA patients and 42 control subjects allocated to either a group treated with atorvastatin (AT) (20 mg/day) or a non-AT group. T(reg) numbers, suppressive function, serum inflammatory markers, and disease activity were evaluated before and after the therapy. Furthermore, the effects of AT on the frequency and suppressive function of T(reg) were determined in vitro. Our data revealed that the suppressive function of T(reg) from RA patients significantly decreased compared with that of control subjects. AT significantly reduced erythrosedimentation, C-reactive protein, and disease activity. Concomitantly, T(reg) numbers and suppressive functions were significantly improved by AT. Consistent with the in vivo experiments, AT promoted the generation of T(reg) from primary T cells and enhanced preexisting T(reg) function in vitro. Moreover, we showed that PI3K-Akt-mTOR and ERK signal pathways were involved in the induction of T(reg) by AT. In conclusion, AT significantly increased T(reg) numbers and restored their suppressive function in the RA patients, and this may be relevant in the modulation of uncontrolled inflammation in this disorder.
authors.affiliation: Laboratory of Cardiovascular Immunology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Tang
authors.forename: You
authors.initials: Y
authors.lastname: Song
authors.forename: Ying-Jun
authors.initials: YJ
authors.lastname: Ding
authors.forename: Yu-Hua
authors.initials: YH
authors.lastname: Liao
authors.forename: Xian
authors.initials: X
authors.lastname: Yu
authors.forename: Rong
authors.initials: R
authors.lastname: Du
authors.forename: Hong
authors.initials: H
authors.lastname: Xiao
authors.forename: Jing
authors.initials: J
authors.lastname: Yuan
authors.forename: Zi-Hua
authors.initials: ZH
authors.lastname: Zhou
authors.forename: Meng-Yang
authors.initials: MY
authors.lastname: Liao
authors.forename: Rui
authors.initials: R
authors.lastname: Yao
authors.forename: Harish
authors.initials: H
authors.lastname: Jevallee
authors.forename: Guo-Ping
authors.initials: GP
authors.lastname: Shi
authors.forename: Xiang
authors.initials: X
authors.lastname: Cheng
mesh_terms: D000328:Adult; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology*; D000069059:Atorvastatin; D005260:Female; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; D011758:Pyrroles; D000069059:Atorvastatin